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. 2022 Sep 2:12:980058.
doi: 10.3389/fonc.2022.980058. eCollection 2022.

[68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma

Peter Truckenmueller  1 , Josefine Graef  2 , Michael Scheel  3 , Peter Vajkoczy  1 , David Capper  4   5 , David Kaul  5   6 , Christian Furth  2 , Holger Amthauer  2 , Winfried Brenner  2 , Julia Sophie Onken  1   5   7
Affiliations

[68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma

Peter Truckenmueller et al. Front Oncol. .

Abstract

Purpose: High-grade gliomas (HGG) are still associated with a dismal prognosis. Prostate specific membrane antigen (PSMA) is discussed as a theranostic target for PSMA-directed radioligand therapy ([177Lu]Lu-PSMA RLT). Here, we report on the correlation of [68Ga]Ga-PSMA uptake with histological PSMA expression and on our preliminary experience with [177Lu]Lu-PSMA RLT in relapsing HGG.

Methods: Patients with relapsing HGG underwent [68Ga]Ga-PSMA PET/MRI to evaluate eligibility for an individualized treatment approach with [177Lu]Lu-PSMA. Standard uptake values (SUV) for tumor and liver and respective tumor-to-background ratios (compared to the liver) (TBR) on [68Ga]Ga-PSMA PET/MRI were assessed. Eligibility criteria for [177Lu]Lu-PSMA therapy were exhaustion of all standard treatment options available and TBRmax>1.0. In 11 samples, immunohistochemical PSMA expression was determined, quantified using the H-score and correlated with uptake on [68Ga]Ga-PSMA PET/MRI.

Results: We included 20 patients with a median age of 53 years (IQR 42-57). The median SUV on [68Ga]Ga-PSMA PET/MRI was 4.5 (3.7-6.2) for SUVmax and 1.4 (1.1-1.7) for SUVmean. The respective TBR was maximum 0.6 (0.4-0.8) and mean 0.3 (0.2-0.4). High TBRmax correlated with increased endothelial PSMA expression [H-score of 65 (62.5-77.5)]. Three patients (15%) presented a TBRmax>1.0 and qualified for [177Lu]Lu-PSMA RLT. No treatment related toxicity was observed.

Conclusion: Only a minority of patients with relapsing HGG qualified for [177Lu]Lu-PSMA RLT. Our data demonstrates that PSMA expression in the neo-vasculature corresponds to PSMA uptake on [68Ga]Ga-PSMA PET/MRI and might be used as a screening tool for patient selection. Future prospective studies need to focus the debate on TBRmax thresholds as inclusion criteria for PSMA RLT.

Keywords: IHC PSMA expression; [177Lu]Lu-PSMA therapy; [68Ga]Ga-PSMA PET/MRI; individualized treatment; relapsing malignant glioma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical PSMA expression in high-grade glioma of three patients eligible for [177Lu]Lu-PSMA therapy. Left column 100x magnification, right column 200x magnification. (A) First patient with increased endothelial PSMA expression with H-score 60 and TBRmax of 1.03 (B) Second patient with increased endothelial PSMA expression with H-score 65 and TBRmax of 1.06 (C) Third patient with increased endothelial PSMA expression with H-score 90 and TBRmax of 1.35.
Figure 2
Figure 2
Correlation and simple linear regression analysis of immunohistochemical PSMA expression and [68Ga]Ga-PSMA uptake of patients eligible and not eligible for [177Lu]Lu RLT. (A) Between endothelial PSMA expression and [68Ga]Ga-PSMA uptake, f = 1.03 and p = 0.34 (B) Between tumor cell PSMA expression and [68Ga]Ga-PSMA uptake, f = 0.17 and p = 0.69.
Figure 3
Figure 3
Swimmer plot showing the time interval between the biopsy with immunohistological PSMA staining and the PSMA PET/MRI in the context of previous therapies and surgeries of the eleven patients with available histological PSMA staining. Each section of the stacked columns reflects the period from beginning a therapy until initiation of the next line therapy. PSMA, prostate specific membrane antigen; 177Lu-RLT, [177Lu]Lu-PSMA RLT.
Figure 4
Figure 4
Illustrative case. (A) Preoperative MRI post contrast enhancement with standard [18F]Fluoro-ethyl-tyrosine (FET) PET/MRI right before open biopsy. (B) In-line view of the open biopsy trajectory. (C) Corresponding PSMA staining of the open biopsy with predominant endothelial PSMA expression. (D) MRI post contrast enhancement with [Ga68]Ga-PSMA PET/MRI only two months after the biopsy with maximum tumor-to-liver ratio of 1.35.
See this image and copyright information in PMC

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